Phenotyping Endometriosis through Mixed Membership Models of Self-Tracking Data

by | Nov 6, 2018 | Research Publications

Author(s):

  • Urteaga, Iñigo
  • McKillop, Mollie
  • Lipsky-Gorman, Sharon
  • Elhadad, Noémie

Abstract:

We investigate the use of self-tracking data and unsupervised mixed-membership models to phenotype endometriosis. Endometriosis is a systemic, chronic condition of women in reproductive age and, at the same time, a highly enigmatic condition with no known biomarkers to monitor its progression and no established staging. We leverage data collected through a self-tracking app in an observational research study of over 2,800 women with endometriosis tracking their condition over a year and a half (456,900 observations overall). We extend a classical mixed-membership model to accommodate the idiosyncrasies of the data at hand (i.e., the multimodality of the tracked variables). Our experiments show that our approach identifies potential subtypes that are robust in terms of biases of self-tracked data (e.g., wide variations in tracking frequency amongst participants), as well as to variations in hyperparameters of the model. Jointly modeling a wide range of observations about participants (symptoms, quality of life, treatments) yields clinically meaningful subtypes that both validate what is already known about endometriosis and suggest new findings.

Document:

https://arxiv.org/abs/1811.03431

References:
  1. Karen Ballard, Karen Lowton, and Jeremy Wright. What’s the delay? A qualitative study of women’s experiences of reaching a diagnosis of endometriosis.Fertility and sterility,86(5):1296–1301, 2006.
  2. David M. Blei. Probabilistic Topic Models.Communications of the ACM, 55(4):77–84,April 2012. ISSN 0001-0782.
  3. David M Blei, Andrew Y Ng, and Michael I Jordan. Latent Dirichlet allocation.Journal of machine Learning research, 3(Jan):993–1022, 2003.
  4. Brian M Bot, Christine Suver, Elias Chaibub Neto, Michael Kellen, Arno Klein, ChristopherBare, Megan Doerr, Abhishek Pratap, John Wilbanks, E Ray Dorsey, et al. The mPowerstudy, Parkinson disease mobile data collected using ResearchKit.Scientific data, 3:160011, 2016.
  5. Yu-Feng Yvonne Chan, Pei Wang, Linda Rogers, Nicole Tignor, Micol Zweig, Steven GHershman, Nicholas Genes, Erick R Scott, Eric Krock, Marcus Badgeley, et al. TheAsthma Mobile Health Study, a large-scale clinical observational study using ResearchKit.Nature biotechnology, 35(4):354, 2017.
  6. Vito Chiantera, Elene Abesadze, and Sylvia Mechsner. How to understand the complexityof endometriosis-related pain.Journal of Endometriosis and Pelvic Pain Disorders, 9(1):30–38, 2017.
  7. Maurice K Chung, Rosemary P Chung, and David Gordon. Interstitial cystitis and en-dometriosis in patients with chronic pelvic pain: The “Evil Twins” Syndrome.JSLS:Journal of the Society of Laparoendoscopic Surgeons, 9(1):25, 2005.
  8. Daniel W Cramer and Stacey A Missmer. Epidemiology of endometriosis. InEndometriosisin Clinical Practice, pages 79–94. CRC Press, 2004.
  9. Elaine Denny and Christopher H. Mann. A clinical overview of endometriosis: a misunder-stood disease.British journal of nursing, 16(18):1112–1116, 2007a.
  10. Elaine Denny and Christopher H. Mann. Endometriosis-associated dyspareunia: the impacton women’s lives.BMJ Sexual & Reproductive Health, 33(3):189–193, 2007b.
  11. Malin Ek, Bodil Roth, Per Ekstr ̈om, Lil Valentin, Mariette Bengtsson, and Bodil Ohlsson.Gastrointestinal symptoms among endometriosis patient’s: A case-cohort study.BMCWomen’s Health, 15(1):59, 2015.
  12. Ronald A Fisher. On the interpretation ofχ2from contingency tables, and the calculationof P.Journal of the Royal Statistical Society, 85(1):87–94, 1922.L Hartsell and K Heller. Preliminary fatigue subtype discovery from the MS mosaic study.InMultiple Sclerosis Journal, volume 23, pages 734–735, 2017.
  13. Stephen T Holgate, Anthony L Komaroff, Dennis Mangan, and Simon Wessely. Chronic fatigue syndrome: understanding a complex illness.Nature Reviews Neuroscience, 12(9):539, 2011.
  14. Kristin J Holoch, Ricardo F Savaris, David A Forstein, Paul B Miller, H Lee Higdon III,Creighton E Likes, and Bruce A Lessey. Coexistence of polycystic ovary syndrome and endometriosis in women with infertility.Journal of Endometriosis and Pelvic Pain Dis-orders, 6(2):79–83, 2014.
  15. Neil P Johnson, Lone Hummelshoj, G David Adamson, J ̈org Keckstein, Hugh S Taylor,Mauricio S Abrao, Deborah Bush, Ludwig Kiesel, Rulla Tamimi, Kathy L Sharpe-Timms,et al. World Endometriosis Society consensus on the classification of endometriosis.Hu-man Reproduction, 32(2):315–324, 2017.
  16. Marina Kvaskoff, Fan Mu, Kathryn L Terry, Holly R Harris, Elizabeth M Poole, LeslieFarland, and Stacey A Missmer. Endometriosis: a high-risk population for major chronic diseases?Human reproduction update, 21(4):500–516, 2015.
  17. Karine Louati and Francis Berenbaum. Fatigue in chronic inflammation-a link to pain pathways.Arthritis research & therapy, 17(1):254, 2015.
  18. Georgina M Luscombe, Robert Markham, Mirari Judio, Ariadna Grigoriu, and Ian S Fraser.Abdominal bloating: an under-recognized endometriosis symptom.Journal of Obstetrics and Gynaecology Canada, 31(12):1159–1171, 2009.
  19. Mollie McKillop, Natalie Voigt, Rebecca Schnall, and No ́emie Elhadad. Exploring self-tracking as a participatory research activity among women with endometriosis.Journal of Participatory Medicine, 2016.
  20. Mollie McKillop, Lena Mamykina, and No ́emie Elhadad. Designing in the Dark: ElicitingSelf-tracking Dimensions for Understanding Enigmatic Disease. InProceedings of the 2018 CHI Conference on Human Factors in Computing Systems, page 565. ACM, 2018.
  21. Fan Mu, Janet Rich-Edwards, Eric B Rimm, Donna Spiegelman, John P Forman, and Stacey A Missmer. Association Between Endometriosis and Hypercholesterolemia orHypertension Novelty and Significance.Hypertension, 70(1):59–65, 2017.
  22. Rimma Pivovarov, Adler J. Perotte, Edouard Grave, John Angiolillo, Chris H. Wiggins,and Nomie Elhadad. Learning probabilistic phenotypes from heterogeneous EHR data.Journal of Biomedical Informatics, 58:156 – 165, 2015. ISSN 1532-0464.
  23. Carley J Pope, Verinder Sharma, Sapna Sharma, and Dwight Mazmanian. A systematicreview of the association between psychiatric disturbances and endometriosis.Journal of Obstetrics and Gynaecology Canada, 37(11):1006–1015, 2015.
  24. Graeme D Ruxton. The unequal variance t-test is an underused alternative to Student’st-test and the Mann–Whitney U test.Behavioral Ecology, 17(4):688–690, 2006.
  25. Sarina Schrager, Julianne Falleroni, and Jennifer Edgoose. Evaluation and treatment of endometriosis.Am Fam Physician, 87(2):107–113, 2013.
  26. S Shabanov, JM Wenger, S Seidler, M Bolmont, F Bianchi-Demicheli, and N Pluchino.When sex hurts the couple: the case of endometriosis.Revue medicale suisse, 13(554):612–616, 2017.
  27. Lisa B Signorello, Bernard L Harlow, Daniel W Cramer, Donna Spiegelman, and Joseph AHill. Epidemiologic determinants of endometriosis: a hospital-based case-control study.Annals of epidemiology, 7(4):267–274, 1997.
  28. Steven Simoens, Gerard Dunselman, Carmen Dirksen, Lone Hummelshoj, Attila Bokor, IrisBrandes, Valentin Brodszky, Michel Canis, Giorgio Lorenzo Colombo, Thomas DeLeire,et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres.Human Reproduction, 27(5):1292–1299, 2012.
  29. EndometriosisJohn Torous, Patrick Staples, Ian Barnett, Luis R Sandoval, Matcheri Keshavan, and Jukka-Pekka Onnela. Characterizing the clinical relevance of digital phenotyping data quality with applications to a cohort with schizophrenia.npj Digital Medicine, 1(1):15, 2018.
  30. P. Vercellini, L. Fedele, G. Aimi, G. Pietropaolo, D. Consonni, and P.G. Crosignani. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients.Human Reproduction, 22(1):266–271, 2007.
  31. Paolo Vercellini, Olga De Giorgi, Giorgio Aimi, Stefania Panazza, Anna Uglietti, andPier Giorgio Crosignani. Menstrual characteristics in women with and without en-dometriosis.Obstetrics & Gynecology, 90(2):264–268, 1997.
  32. Allison F Vitonis, Katy Vincent, Nilufer Rahmioglu, Amelie Fassbender, Germaine M BuckLouis, Lone Hummelshoj, Linda C Giudice, Pamela Stratton, G David Adamson, Chris-tian M Becker, et al. World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: II. Clinical and covariate phenotype data collection in endometriosis research.Fertility and sterility, 102(5):1223–1232, 2014.
  33. Hanna M Wallach, Iain Murray, Ruslan Salakhutdinov, and David Mimno. Evaluation
  34. Methods for Topic Models. InProceedings of the 26th Annual International Conference on Machine Learning, ICML ’09, pages 1105–1112, New York, NY, USA, 2009. ACM.ISBN 978-1-60558-516-1.Pamela E Warner, Hilary OD Critchley, Mary Ann Lumsden, Mary Campbell-Brown, Anne Douglas, and Gordon D Murray. Menorrhagia I: measured blood loss, clinical features, and outcome in women with heavy periods: a survey with follow-up data.American journal of Obstetrics & Gynecology, 190(5):1216–1223, 2004.
  35. JM Wheeler. Epidemiology of endometriosis-associated infertility.The Journal of reproductive medicine, 34(1):41–46, 1989.
  36. Meng-Han Yang, Peng-Hui Wang, Shuu-Jiun Wang, Wei-Zen Sun, Yen-Jen Oyang, and Jong-Ling Fuh. Women with endometriosis are more likely to suffer from migraines: a population-based study.PLoS One, 7(3):e33941, 2012.
  37. Andong Zhan, Srihari Mohan, Christopher Tarolli, Ruth B Schneider, Jamie L Adams,Saloni Sharma, Molly J Elson, Kelsey L Spear, Alistair M Glidden, Max A Little, et al.Using Smartphones and Machine Learning to Quantify Parkinson Disease Severity: TheMobile Parkinson Disease Score.JAMA neurology, 2018